The proposed work deals with the controls underlying differential gene expression during eukaryotic development. The time and tissue specific production of selected enzymes in Drosophila are taken as models of this differential gene expression. Enzymes are selected on the basis of biochemical convenience, availability of useful genetic markers and developmental specificity. The principal goal of the work is to obtain and characterize mutations that alter normal patterns of expression. Genes with a major effect or expression of an enzyme that do not alter its primary structure are presumed to identify loci that are "regulatory" in some sense. It is hoped that information on the types of "regulatory" mutants found, their organization relative to the affected structural gene and each other and their interactions when placed in combination will contribute to the formulation and testing of models of gene regulation in eukaryotes as it has in prokaryotes. On the basis of previous work in this and other laboratories, we propose that existing variability in the patterns of enzyme expression within and between Drosophila populations is a useful source of "regulatory" variants. We intend to continue genetic and biochemical analysis of putative regulatory variants now in hand, search for new variants utilizing a design that will also yield some data on the frequency of occurrence of such variants in existing stocks and extend our methods to selected additional enzymes to test the generality of our findings.